DNA methylome signature in rheumatoid arthritis.
DNA methylome signature in rheumatoid arthritis.
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DOI：
10.1136/annrheumdis-2012-201526
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发表时间：
2013-01
影响因子：
27.4
通讯作者：
Firestein GS
中科院分区：
文献类型：
--
作者：
Nakano K;Whitaker JW;Boyle DL;Wang W;Firestein GS
表观遗传学可以影响疾病的易感性和严重性。虽然已在自身免疫中探索了单个基因的DNA甲基化，但尚未报道无偏见的系统分析。因此，从类风湿性关节炎（RA）的疾病部位分离的成纤维细胞样滑膜细胞（FLS）的DNA甲基化位点的全基因组评估。从六个RA和五个骨关节炎（OA）FLS系中分离基因组DNA，并使用Illumina HumanMethylation 450芯片进行评估。对数据进行聚类分析，并使用Benjamini-Hochberg校正进行多重比较。通过焦磷酸测序确认甲基化，并通过qPCR测定基因表达。使用京都基因和基因组百科全书进行途径分析。RA和对照FLS基于DNA甲基化分离，具有1859个差异甲基化位点。在与RA相关的关键基因CHI 3L 1、CASP 1、STAT 3、MAP 3 K5、MEFV和WISP 3中发现了低甲基化位点。还观察到了高甲基化，包括TGFBR 2和FOXO 1。个别基因的低甲基化与基因表达增加有关。分组分析发现了207个高甲基化或低甲基化的基因，其中包括COL 1A 1、MEFV和TNF。低甲基化在与细胞迁移相关的多种途径中增加，包括粘着斑、细胞粘附、跨内皮迁移和细胞外基质相互作用。对OA和正常FLS的验证性研究也证明了基于甲基化模式的RA与对照FLS的分离。FLS基因甲基化程度的差异可能与RA的发病机制有关。关键基因的DNA甲基化表明RA FLS是印记的，并涉及炎症性关节炎的表观遗传贡献。
Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini–Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis.
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影响因子：
5.5
作者：
Inazuka, M;Tahira, T;Hayashi, K
通讯作者：
Hayashi, K
影响因子：
4.9
作者：
Da Sylva TR;Connor A;Mburu Y;Keystone E;Wu GE
通讯作者：
Wu GE
影响因子：
4.4
作者：
Lee, SH;Chang, DK;Firestein, GS
通讯作者：
Firestein, GS
DOI：
10.1084/jem.20101438
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Christophersen NS;Helin K
通讯作者：
Helin K
影响因子：
--
作者：
Bang, Holger;Egerer, Karl;Burmester, Gerd-R.
通讯作者：
Burmester, Gerd-R.